6. Project Summary/Abstract Traumatic brain injury (TBI) is a leading cause of morbidity and disability in service members deployed in Iraq and Afghanistan, accounting for one-fourth of medical evacuations. An explosive mechanism was linked to 78% of the clinician-confirmed injuries sustained by U.S. service members over a three-year period, and the head and neck were involved in 30% of these injuries. To elucidate the neural mechanisms mediating cognitive deficit after blast related TBI, we propose to perform multimodality brain imaging, cognitive, behavioral and health related quality of life outcome measures in veterans and service members who sustained TBI due to blast while deployed in Iraq or Afghanistan. A total of 84 veterans and service members will be enrolled between 4 and 60 months post-injury, including 28 who sustained moderate to severe blast related TBI, 28 with mild blast related TBI, and a comparison group who sustained injury not involving the brain. Functional magnetic resonance imaging (fMRI) will be performed during cognitive control and working memory tasks and analyzed in relation to the integrity of brain gray matter and white matter measured by magnetization transfer imaging and diffusion tensor imaging and brain region volumes measured by magnetic resonance imaging (MRI). We will also analyze fMRI data adjusting for co-morbid posttraumatic stress disorder and depression symptoms. With this design we propose to evaluate the effects of blast related TBI on brain function in relation to indices of brain structural integrity and co-morbidities of injury. PUBLIC HEALTH RELEVANCE: Project Narrative This renewal project uses multimodality brain imaging to characterize brain function following blast related traumatic brain injury (TBI) in veterans and service members. Using functional magnetic resonance imaging (fMRI) while veterans and service members with moderate to severe (n=28) or mild (n=28) blast related TBI perform cognitive control and working memory tasks, we propose to analyze the results in relation to structural brain integrity as measured by brain region volumes, diffusion tensor imaging, and magnetization transfer imaging. Analysis of fMRI will also adjust for co-morbid posttraumatic stress disorder and depression. A group of 28 veterans and service members who sustained injury not involving the brain will also be studied for comparison with the TBI groups.